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Hyalinizing cholecystitis is a rare type of chronic cholecystitis. Moderate patchy transmural especially perivascular lymphoplasmacytic inflammatory cell infiltration is observed in the gallbladder wall. We present the 18F-FDG PET/CT and MRI findings of this rare subtype of chronic cholecystitis. Hyalinizing cholecystitis should be kept in mind in the differential diagnosis of gallbladder wall thickening with intense 18F-FDG uptake.

Objective To investigate the effect and mechanism of interleukin (IL)-17C in mice undergoing kidney transplantation. Methods The life-supporting kidney transplantation mice models were established using Balb/c (H-2Kd) mice as the donors, IL-17C gene knock out (IL-17CKO) mice (knockout group) and C57BL/6J(H-2Kb) mice (wild group) were chosen as the recipients. The postoperative body mass and survival time of mice were statistically compared between two groups. Pathological examination of the kidney graft was performed by using hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining. The expression levels of granzyme B, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6 and IL-1β messenger ribonucleic acid (mRNA) in the kidney graft tissue were quantitatively measured by reverse transcription polymerase chain reaction (RT-PCR). The proportion of inflammatory cell infiltration in the kidney graft tissue was detected by flow cytometry. Results In the knockout group, the survival time of mice after kidney transplantation was significantly shorter than that of the wild mice (P=0.031). The body mass was more evidently decreased in the knockout group with no statistical significance from that in the wild group. Pathological examination demonstrated that the kidney graft injury in the knockout group was significantly worse than that in the wild group. The mRNA expression levels of granzyme B, IFN-γ, TNF-α, IL-6 mRNA in the knockout group were significantly up-regulated compared with those in the wild group (all P < 0.01). The mRNA expression level of IL-1β showed a decreasing trend with no statistical significance (P=0.16). Flow cytometry analysis revealed that the infiltration of CD45+CD11b+Ly6G+ neutrophil and CD45+CD11b+Ly6Chi monocyte in the kidney graft of knockout mice was significantly higher compared with that of the wild mice (P < 0.05, P < 0.01), whereas the infiltration of CD45+Ly6ChiF4/80+ macrophage did not significantly differ between two groups (P > 0.05). Conclusions IL-17C participates in the regulation of inflammatory response after kidney transplantation. It can alleviate acute rejection and improve the survival of kidney graft by down-regulating the expression of pro-inflammatory cytokines and infiltration of inflammatory cells.

Asthma is a complex and heterogeneous inflammatory response characterized by various immune cells, including myeloid-derived suppressor cells (MDSCs) and CD4+ T-cell subsets. However, few studies on MDSC subsets and the association between MDSCs and CD4+ T-cell subsets in asthma are reported. In the present study, we detected CD4+ T cells and MDSC subsets and evaluated the relationship of these cells in mice with ovalbumin-induced asthma. We found that asthmatic mice showed severe airway inflammatory response and inflammatory cell infiltration in the lungs and bronchoalveolar lavage fluid. We also noted increased numbers of Th2, Th17, and MDSCs; decreased proportion of Th1 and Treg cells in the splenocytes and lungs; and increased expression of pro-inflammatory cytokines in splenocytes and lungs. Granulocytic MDSCs (G-MDSCs) and Th17 cells were closely related. Gemcitabine treatment reduced the G-MDSC level and the iNOS expression, alleviated the inflammatory response, and decreased the proportion and number of Th2 and Th17 cells in asthmatic mice. Besides the increase in Th2 and Th17 cells, the findings indicate that G-MDSC elevation plays a crucial role in asthmatic mice.

Aim:The purpose of this study was to determine whether extremely low frequency electric and magnetic field (ELF-EMF) had any detrimental effects on periodontal tissue and to investigate, histologically and immunohistochemically whether melatonin (MLT) and Ganoderma lucidum (GL) had a protective role against these detrimental effects. Methodology:A total of 56 adults, male Wistar Albino rats were used in this study. Rats were divided into 7 equal groups and exposed to ELF-EMF, which was produced by a high voltage source, 8 hours / day for 26 days. GL (20 mg / kg / day) and MLT (10 mg / kg / day) were administered by the oral gavage and intraperitoneal method. Results: Fibrous degeneration in the periodontal membrane, inflammatory cell infiltration, connective tissue fiber organization, dilation, and hemorrhage in the blood vessels changes were determined in the periodontal tissue of the rats in groups I and IV. A statistically significant difference was determined in the groups treated with MLT and GL (p

Objective: The aim of this study was to determine whether oak root extract has protective role on burn injuries by using quantitative and histopathological approaches. Material and method: The study was conducted on 16 adult Sprague-Dawley rats aged 8 weeks (weighing 350 g). The rats were assigned into 2 groups including: group 1 consisting of rats employed as controls and group 2 in which rats received oak root extract. After shaving dorsum of rats, second degree burn injury was created at the right and left sides of the line representing vertebral column in both groups. Wound care was provided by using normal saline in group 1, while it was provided by using oat root extract in group 2. The right side was used for macroscopic evaluations, while left side was used for histopathological examination through biopsy samples obtained on the days 1, 3, 7 and 17. On the day 17, the rats were sacrificed under ketamine anesthesia. Cutaneous tissue samples were taken and macroscopic measurements were made by using a grid paper. Edema, neovascularization, inflammatory cell infiltration and re-epithelization were assessed on the histopathological examination. Results: When compared to the control group, it was seen that the extent of burn area was reduced and that degree of neovascularization, inflammatory cell infiltration and re-epithelization was increased with decreased edema was (p

In the current study, the hydatid cyst-induced tissue lesions in liver and lung of camels and sheep infected with Egyptian strain of E. granulosus was evaluated and the fine structures of the protoscolices by scanning electron microscope (SEM) was described. The results indicated that both fertile and sterile hydatid cysts could lead to various degree of tissue lesions visualized mainly as necrosis, inflammatory cell infiltration and tissue degeneration other histopathological changes occurred in lung and liver of infected animals due to infection with hydatid cyst. Tissue lesion associated with hydatidosis was described. SEM showed envaginated, invaginated protoscolex and the broad capsule of hydatid cyst. There were two types of hooks, large (upper row) and small (lower row) in hydatid cyst protoscolices; with microtriches on different regions.

Spinal cord injury (SCI) is a devastating and complicated condition with no cure available. The initial mechanical trauma is followed by a secondary injury characterized by inflammatory cell infiltration and inhibitory glial scar formation. Due to the limitations posed by the blood–spinal cord barrier, systemic delivery of therapeutics is challenging. Recent development of various nanoscale strategies provides exciting and promising new means of treating SCI by crossing the blood–spinal cord barrier and delivering therapeutics. As such, we discuss different nanomaterial fabrication methods and provide an overview of recent studies where nanomaterials were developed to modulate inflammatory signals, target inhibitory factors in the lesion, and promote axonal regeneration after SCI. We also review emerging areas of research such as optogenetics, immunotherapy and CRISPR-mediated genome editing where nanomaterials can provide synergistic effects in developing novel SCI therapy regimens, as well as current efforts and barriers to clinical translation of nanomaterials.

The aims of this research was looked to determine the healing process of burns Grade II B using a mixture of fresh and dried leaf kedondong with vaseline white rats (Rattus norvegicus). Animals used were 18 rats. This study was designed using three treatment groups namely (KI) vaseline, (KII) mixture of crushed leaves and fresh kedondong (KIII) mixture of crushed dried leaves kedondong and each two replications. Burns made on the backs of mice and the treatments are done twice a day for 21 days.Observation research parameter is the description of macroscopic and microscopic observed at day 7, 14, and 21 in the skin tissue with hematoxylin and eosin staining. The observation of macroscopic studies showed that the formation of a reddish color, presence of edema, and loss of the fastest consecutive scab is KI, KIII, and KII, while the formation of a scab fastest respectively KIII, KI and KII. The observation of histopathology showed on day 7, KI, KII and KIII found inflammatory cell infiltration, hemorrhage and edema with the spread of many.on the 14th day of KI and KII infiltration of inflammatory cells and their udema much, whereas KIII inflammatory cell infiltration decreased, and hyperemia increase, on the 21st day KI, KII and KII inflammatory cell infiltration, hyperemia and hemorrhage spread with a little, but KI and KII oedemanya still being spread. Based on the results of this study concluded that KIII accelerate the healing process of burns on rats

BACKGROUND Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is one of the most studied immune checkpoint in gastric cancer (GC). However, the prognostic role of CTLA-4 expression in GC is poorly described. This study aimed to evaluate CTLA-4 expression in GC and its impact on survival, including patients treated with standard platinum-based chemotherapy (CMT), and association with PD-L1 expression. METHODS All GC patients who underwent D2-gastrectomy were investigated retrospectively. Tumor samples were examined for CTLA-4 and PD-L1 by immunohistochemistry. Tumor-infiltrating inflammatory cells, including CD4 + and CD8 + , were also examined. RESULTS Among the 284 GC patients included, 159 (56%) were CTLA-4 positive and the remaining 125 (44%) were classified as negative. CTLA-4 positive GC was associated with increased inflammatory cell infiltration (p

IntroductionCC chemokine receptor 5 (CCR5) and the NF-κB signaling pathway play important roles in the pathophysiology of inflammatory bowel disease (IBD). Previously, we synthesized two peptides (GH and HY peptides) that specifically bind to the first and the second extracellular loops (ECL1 and ECL2, respectively) of CCR5 and preliminarily found an inhibitory effect of these peptides on colitis. However, the specific mechanism by which these two peptides regulate trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats remains unclear.Material and methodsExperimental colitis was induced by 5% TNBS. CCR5 antagonist peptides were administered intravenously once a day for a week. Histological evaluation, real-time PCR, western blotting and correlation analysis were performed to examine the effects of the CCR5 binding peptides on the infiltration of inflammatory cells and the NF-κB signaling pathway.ResultsGH and HY peptides ameliorated mucosal damage and reduced the infiltration of neutrophils, lymphocytes and macrophages in experimental colitis (P < 0.05). The expression of NF-κB-related genes, including p105, p100, IKK and TNF-α, was reduced after GH and HY peptide administration (P < 0.01), and the protein level of TNF-α and the phosphorylation of IKK, IκBα and p65 were also suppressed. Furthermore, CCR5 antagonist peptides inhibited nuclear translocation of p65. Spearman correlation analysis showed that the infiltration of inflammatory cells was significantly correlated with the NF-κB pathway.ConclusionsAntagonistic peptides that specifically bind to ECL1 and ECL2 of CCR5 inhibit the infiltration of neutrophils, lymphocytes and macrophages in the colonic mucosa of SD rats with TNBS-induced colitis via regulation of the NF-κB signaling pathway.

Pruritus pigmentosa is a skin disease mainly characterized by pruritus, inflammatory rash and reticular and macular pigmentation. The disease more commonly affects young women and may persist for several years. In this article, we report a case of a 20-year-old female patient who presented with erythema and blisters on the neck and trunk with pruritus for 20 days. Dermatological examination revealed a reticular distribution of erythema on the chest and abdomen and some areas of erythema covered with crusts. Additionally, blisters and bullae with clear fluid and negative Nikolsky’s sign were noted. On the neck and back, erythema was also in a reticular distribution, and erythema secondary to erosion and/or crusts was present. In addition, histopathological analysis of the lesions showed hyperkeratosis and intraepidermal multilocular vesiculation and confirmed increased migration of inflammatory cells into the epidermis and infiltration of inflammatory cells, including lymphocytes, histiocytes and eosinophils, in the superficial dermis. The expression levels of IgG, IgM, IgA and C3 were all negative. This patient was diagnosed with prurigo pigmentosa, and the condition improved after treatment with minocycline.

P2X7R is a vital modifier of various inflammatory and immune-related diseases. However, the immunomodulatory effects of P2X7R on corneal allograft rejection remains unknown. Here we showed that P2X7R expression was significantly upregulated in corneal grafts of allogeneic transplant mice. Pharmacological blockage of P2X7R remarkably prolonged graft survival time, and reduced inflammatory cell infiltration in corneal grafts, in particular Th1/Th17 cells. Meanwhile, the frequencies of Th1/Th17 cells in draining lymph nodes were significantly decreased in P2X7R blocked allogeneic mice. Further results showed that the effect of P2X7R on promoting Th1/Th17 mediated immune responses in corneal allograft rejection relied heavily on its activation on the NLRP3/caspase-1/IL-1β axis, while P2X7R blockage could mitigate such activation. Nevertheless, the addition of IL-1β in vivo abrogated the protective effect of P2X7R blockage on promoting corneal graft survival. These findings demonstrate that blockage of P2X7R can substantially alleviate corneal allograft rejection and promote grafts survival, highlighting it as a promising target for preventing or treating corneal allograft rejection.

Los especímenes de museo representan un recurso valioso para la investigación helmintológica. Hemos examinado los hígados fijados en formalina conservados por períodos de más de 50 años a partir de cerdos infectados naturalmente en el material de archivo de la Colección Helmintológica del Instituto Oswaldo Cruz (CHIOC), Fundación Oswaldo Cruz (FIOCRUZ). El examen microscópico reveló evidencia de parásitos en estructuras quísticas uniloculares que contienen una vesícula de la membrana del parásito recubierto con una lámina delgada. La capa interna germinal contiene los restos del parásito y un líquido proteíco como hidatídico. El parénquima hepático mostró un denso infiltrado inflamatorio cerca del quiste, los vasos arteriales de paredes gruesas y necrosis de vez en cuando. El parénquima hepático adyacente mostró fibrosis delgada inter e intralobular, la infiltración de células inflamatorias y necrosis de vez en cuando. Otros cortes histológicos mostraron una estructura de pared gruesa laminada quística con cápsulas de cría en la capa germinal que contienen proyecciones pequeñas y redondas con el centro de las vesículas internas en la superficie interna, lo que sugiere la presencia de protoescólices. Teniendo en cuenta que Echinococcus multilocularis no ocurre en Brasil, nuestros hallazgos histológicos fueron identificados como Echinococcus granulosus de origen. En conclusión, el protocolo que se presenta en este estudio pone de relieve la posibilidad de lograr resultados histológicos de muy alta calidad en archivos fijados en formalina y parafina de tejidos embebidos recuperados de especímenes de museo que se han conservado durante muchos años.

Acne is a common skin disease that occurs in pilosebaceous units and is often prevalent in adolescence. There are many acne treatments, but they are associated with side effects, such as antibiotic resistance, teratogenicity, and irritation. Therefore, it is necessary to develop a more effective and safe alternative treatment for managing acne in patients of all ages. This study aimed to confirm the effect of gold photothermal therapy for acne. About 12 patients who visited the dermatologic clinic with moderate to severe acne vulgaris were included in the study, regardless of age or sex. All patients received three successive treatments at 1- to 2-week intervals with a photopneumatic device after applying the contents of a gold nanoparticle ample to the skin. Changes in the number of papules, pustules, and comedones before and after treatment, along with the overall improvement, were assessed. In four patients, a biopsy was taken before and 1 month after the last treatment. Significant reductions in acne lesions were observed after the use of gold photothermal therapy (papules, P = .001; pustules, P

BackgroundImmunoglobulin G4 (IgG4)-related diseases are characterized by abnormal IgG4 levels, swelling, and marked infiltration and fibrosis of the lymphocytes and IgG4-positive plasma cells, causing hypertrophic lesions or nodules. The cause is currently not well understood. IgG4-related diseases involving lesions limited to the pleura are extremely rare. Herein, we report an IgG4-related disease presenting with multiple pleural nodules confirmed by thoracoscopic surgical biopsy.Case presentationA 74 year-old man was referred to our department for definitive diagnosis of multiple pleural nodules after 1 year of follow-up. Computed tomography of the chest revealed multiple pleural nodules, while 2-deoxy-2-(18F)-fluorodeoxyglucose positron emission tomography imaging exhibited tracer accumulation in the nodules. A thoracoscopic surgical biopsy was performed. Histopathological examination revealed hyalinized fibrous tissue with a high degree of plasma cell-based inflammatory cell infiltration. Immunohistochemically, IgG4-positive cells were conspicuous, accounting for 70.5% of the plasma cells. The postoperative serum IgG4 concentration was 289 mg/dL. We diagnosed the patient with an IgG4-related disease with multiple pleural nodules. The postoperative course was good, and the patient is currently being followed up.ConclusionIgG4-related disease should be considered in cases presenting with multiple pleural nodules.

There is a clinical need to develop a stent to treat obstructive and refractory Eustachian tube dysfunction (ETD) after balloon Eustachian tuboplasty. An animal model for stent placement in the Eustachian tube (ET) is needed to develop optimal designs and materials, as stents for ETD have not been clinically applied. The purpose of this study was to evaluate the technical feasibility of stent placement and histological changes in a porcine ET model. Six ETs were evaluated in three pigs. Cobalt–chrome alloy stents with two different diameters were placed in the left and right ET of each animal (right, 3.5 mm, left, 2.5 mm). The outcomes were assessed by endoscopic and fluoroscopic imaging during the procedure, computed tomography after the procedure, and by histological examinations. Stent placement was technically successful in all specimens after metallic guiding sheaths were located in the nasopharyngeal end of the ET. The mean luminal diameters of the proximal, middle, and distal portions of the larger stents in the right ETs were 3.48 mm, 2.54 mm, and 2.15 mm, respectively. In the left ETs using smaller stents, these values were 2.49 mm, 1.73 mm, and 1.42 mm, respectively. The diameters of the inserted stents differed by stent location and the original diameter. Histological findings showed tissue hyperplasia with severe inflammatory cell infiltration at 4 weeks after stent placement. In conclusion, stent placement into the porcine ET was technically feasible, and stent-induced tissue hyperplasia was significantly evident. The luminal configuration of the placed ET stent changed according to its non-elastic nature and anatomical features of the porcine ET. Using this model, ET stents of various materials and designs with anti-inflammatory or anti-proliferative drugs can be optimized for future treatments of ET dysfunction.

This study was conducted in order to investigate biological compatibility of a thin and flexible hydroxyapatite (HAP) paper which consists of ultralong hydroxyapatite nanowires. Circular-shaped cranial bone defects with a diameter of 8.8 mm were prepared to expose the dura maters in Wistar rats. The similar-sized, circular-shaped HAP paper was placed at the bottom of the bone defects. After 2, 4, and 8 weeks, the rats were sacrificed, and the experimental sections were examined by micro-CT scanning and histological observation. The HAP paper covered with fibrous tissues showed no inflammatory cell infiltration, and their thicknesses decreased over time. Tartrate-resistant acid phosphatase-positive osteoclast-like cells were induced around the edges of the HAP paper along with the exfoliation of the HAP paper. The newly-formed bones were observed in the bone-defected areas, either with a direct contact with the HAP paper or through thin fibrous tissues. The HAP paper-induced osteoblast differentiation was confirmed since the alkaline phosphatase activities were detected on the surfaces of the HAP paper. These results indicated that the HAP paper may induce osteogenesis without causing any harmful effects. The highly flexible HAP paper can contribute to further development of bone regenerative therapy.

Background. ML171 is a potent nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor with isoform selectivity only for NOX1. This study is aimed at investigating the safety of ML171 after a single intraperitoneal (IP) injection in mice. Methods. The toxicity of a single dose of ML171 was evaluated in 6-week-old Institute of Cancer Research (ICR) mice in a good laboratory practice (GLP) laboratory. Twenty-five mice of each sex were assigned to five groups: negative control, vehicle control, and 125, 250, and 500 mg/kg of ML171. All mice were acclimatized for one week before beginning the study. Mice received an IP injection of ML171 or vehicle. The general condition and mortality of the animals were observed. The mice were sacrificed to evaluate histopathology 14 days after the administration of ML171 or vehicle. Results. Bodyweights were not significantly different in any group. Three males and one female died due to ML171 administration in the 500 mg/kg dose group. Autopsies of the surviving mice did not reveal any significant abnormalities after the injection of 125 mg/kg of ML171. However, the anterior lobe edge of the liver was thickened and adhesions between the liver and adjacent organs were observed in mice treated with 250 or 500 mg/kg of ML171. In addition, hypertrophy of centrilobular hepatocytes and inflammatory cell infiltration were observed after injection of 250 and 500 mg/kg of ML171. Conclusion. Our results indicate that the lethal IP injection dose of ML171 is 500 mg/kg for both males and females. Mortality were not observed for lower doses of ML171. The safe dose of single IP ML171 in ICR mice was 250 mg/kg or less. Further studies are needed to confirm the safety of ML171 in the human body.

Vascular smooth muscle cell (VSMC) apoptosis is a major defining feature of abdominal aortic aneurysm (AAA) and mainly caused by inflammatory cell infiltration. Smooth muscle (SM) 22α prevents AAA formation through suppressing NF-κB activation. However, the role of SM22α in VSMC apoptosis is controversial. Here, we identified that SM22α loss contributed to apoptosis of VSMCs via activation of macrophages. Firstly, deficiency of SM22α enhanced the interaction of VSMCs with macrophages. Macrophages were retained and activated by Sm22α-/- VSMCs via upregulating VCAM-1 expression. The ratio of apoptosis was increased by 1.62-fold in VSMCs treated with the conditional media (CM) from activated RAW264.7 cells, compared to that of the control CM ( P < 0.01 ), and apoptosis of Sm22α-/- VSMCs was higher than that of WT VSMCs ( P < 0.001 ). Next, circRasGEF1B from activated macrophages was delivered into VSMCs promoting ZFP36 expression via stabilization of ZFP36 mRNA. Importantly, circRasGEF1B, as a scaffold, guided ZFP36 to preferentially bind to and decay Bcl-2 mRNA in a sequence-specific manner and triggered apoptosis of VSMCs, especially in Sm22α-/- VSMCs. These findings reveal a novel mechanism by which the circRasGEF1B-ZFP36 axis mediates macrophage-induced VSMC apoptosis via decay of Bcl-2 mRNA, whereas Sm22α-/- VSMCs have a higher sensitivity to apoptosis.

This study aimed to evaluate and compare the effectiveness of a newly developed epithelial removal brush with conventional methods in a rabbit model of corneal epithelial defects. The corneal epithelia of thirty-seven rabbits were removed by three different methods including blades (blade group), newly developed epithelial brushes (Ocu group), and conventional rotating brushes (Amo group). The defect area was measured with light microscopy immediately and at 4, 18, 24, and 50 hours after removal. Corneas were obtained immediately and at 24 and 50 hours and subjected to hematoxylin and eosin (H&E) and immunofluorescence staining using proliferating cell nuclear antigen (PCNA) and phosphorylated heat shock protein 27 (pHSP27) antibodies. The residual stromal surface was observed by scanning electron microscopy (SEM). In the Ocu group, epithelia were significantly recovered at 18, 24, and 50 hours compared with immediately after removal, and in the blade and Amo groups, epithelia were significantly recovered only at 50 hours after epithelial removal. The expression levels of PCNA and pHSP27 did not differ among three groups. There was significantly more inflammatory cell infiltration in the blade group than in the other groups. SEM showed a more regular and uniform residual stromal surface in the Ocu group than in the other groups. The newly developed epithelial brush showed better polishing ability and led to earlier significant epithelial recovery and a more regular and uniform stromal surface than conventional methods in this rabbit model of epithelial defects. Accumulation of clinical data is expected to expand the scope of application of new brushes for laser surface ablation.

Pulpitis is a frequent bacterially driven inflammation featured with the local accumulation of inflammatory products in human dental pulps. A GEO dataset GSE16134 comprising data of inflamed dental pulp tissues was used for bioinformatics analyses. A protein-protein interaction (PPI) analysis suggested that chemokine receptor 4 (CXCR4) owned a high correlation with platelet endothelial cell adhesion molecule-1 (PECAM1). A rat model with pulpitis was established, and lipopolysaccharide (LPS)-induced human dental pulp fibroblasts (HDPFs) were used for in vitro experiments. Then, high expression of PECAM1 and CXCR4 was validated in the inflamed dental pulp tissues in rats and in LPS-induced HDPFs. Either downregulation of PECAM1 or CXCR4 suppressed inflammatory cell infiltration in inflamed tissues as well as the inflammation and apoptosis of HDPFs. A transcription factor myocyte-enhancer factor 2 (MEF2C) was predicted and validated as a positive regulator of either PECAM1 or CXCR4, which activated the NF-κB signaling pathway and promoted pulpitis progression. To sum up, this study suggested that MEF2C transcriptionally activates PECAM1 and CXCR4 to activate the B-cell and NF-κB signaling pathways, leading to inflammatory cell infiltration and pulpitis progression.

Perivascular adipose tissue (PVAT) has been identified to have significant endocrine and paracrine functions, such as releasing bioactive adipokines, cytokines, and chemokines, rather than a non-physiological structural tissue. Considering the contiguity with the vascular wall, PVAT could play a crucial role in the pathogenic microenvironment of atherosclerosis. Growing clinical evidence has shown an association between PVAT and atherosclerosis. Moreover, based on computed tomography, the fat attenuation index of PVAT was verified as an indication of vulnerable atherosclerotic plaques. Under pathological conditions, such as obesity and diabetes, PVAT shows a proatherogenic phenotype by increasing the release of factors that induce endothelial dysfunction and inflammatory cell infiltration, thus contributing to atherosclerosis. Growing animal and human studies have investigated the mechanism of the above process, which has yet to be fully elucidated. Furthermore, traditional treatments for atherosclerosis have been proven to act on PVAT, and we found several studies focused on novel drugs that target PVAT for the prevention of atherosclerosis. Emerging as an indication, contributor to, and therapeutic target for atherosclerosis, PVAT warrants further investigation.

Objective This study aimed to evaluate the effect of direct pulp capping using an experimental self-adhesive resin for direct pulp capping (SRD) containing silica and surface pre-reacted glass-ionomer (S-PRG) filler on pulpal healing and to monitor the dentin bridge formation in rat pulp 2–4 weeks after operation. Methods Five types of SRDs (SRD-0: S-PRG fillers 0 wt%; SRD-1: S-PRG fillers 9.1 wt%; SRD-2: S-PRG fillers 18.4 wt%; SRD-3: S-PRG fillers 27.8 wt%; and SRD-6: S-PRG fillers 57.4 wt%) were prepared, and mineral trioxide aggregate (MTA) was used as control (n = 8). Direct pulp capping was performed on rats that were sacrificed for further evaluation 2 or 4 weeks after the operation. The pulp tissue disorganization (PTD), inflammatory cell infiltration (ICI), and reparative dentin formation were histopathologically evaluated; the data were statistically analyzed using the Kruskal–Wallis and the Mann–Whitney U tests. Results The histopathological evaluation of SRD-1-treated test animals 2 weeks post-operation revealed inferior PTD and ICI when compared with that of MTA. Even 4 weeks after the operation in SRD-1- and SRD-2-treated rats, the PTD and ICI were inferior when compared with those of MTA. The dental specimens of SRD-0 and MTA showed orthodentin formation, whereas SRD-treated test animals showed osteodentin formation at a position slightly deeper than the site of the pulpal exposure. Significance The reparative dentin formed by SRD-0 and MTA was genuine, whereas that formed by SRD-3 and SRD-6 was ossified and ectopic. SRD may have the potential to be utilized clinically as a direct pulp capping material.

Wang-Jia Li,1,* Fa-Jin Lv,1,* Yi-Wen Tan,2 Bin-Jie Fu,1 Zhi-Gang Chu1 1Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhi-Gang ChuDepartment of Radiology, The First Affiliated Hospital of Chongqing Medical University, 1# Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, People’s Republic of ChinaTel +86 18723032809Fax +86 23 68811487Email chuzg0815@163.comBackground: Some pulmonary ground-glass nodules (GGNs) are benign and frequently misdiagnosed due to lack of understanding of their CT characteristics. This study aimed to reveal the CT features and corresponding pathological findings of pulmonary benign GGNs to help improve diagnostic accuracy.Patients and Methods: From March 2016 to October 2019, patients with benign GGNs confirmed by operation or follow-up were enrolled retrospectively. According to overall CT manifestations, GGNs were classified into three types: I, GGO with internal high-attenuation zone; II, nodules lying on adjacent blood vessels; and other type, lesions without obvious common characteristics. CT features and pathological findings of each nodule type were evaluated.Results: Among the 40 type I, 25 type II, and 14 other type GGNs, 24 (60.0%), 19 (76.0%), and 10 (71.4%) nodules were resected, respectively. Type I GGNs were usually irregular (25 of 40, 62.5%)with only one high-attenuation zone (38 of 40, 95.0%)(main pathological components: thickened alveolar walls with inflammatory cells, fibrous tissue, and exudation), which was usually centric (24 of 40, 60.0%), having blurred margin (38 of 40, 95.0%), and connecting to blood vessels (32 of 40, 80.0%). The peripheral GGO (main pathological component: a small amount of inflammatory cell infiltration with fibrous tissue proliferation) was usually ill-defined (28 of 40, 70.0%). Type II GGNs (main pathological components: focal interstitial fibrosis with or without inflammatory cell infiltration) lying on adjacent vessel branches were usually irregular (19 of 25, 76.0%) and well defined (16 of 25, 64.0%) but showed coarse margins (15 of 16, 93.8%). Other type GGNs had various CT manifestations but their pathological findings were similar to that of type II.Conclusion: For subsolid nodules with CT features manifested in type I or II GGNs, follow-up should be firstly considered in further management.Keywords: ground-glass nodule, benignity, CT, pathology, lung

Biofluorescence in living entities is a functional process associated with information conveyance; whereas the capacity to respond to internal physiological signals is a unique property of a cell. By integrating these two biological features into materials design, a bioinspired material, namely CPS, is developed. Contrary to conventional luminescent polymeric systems whose emission comes from π-conjugated structures, this material displays clusterization-triggered emission. In the preclinical trial on a dermal punch model of tissue repair, it successfully increases the rate of wound closure, reduces inflammatory cell infiltration, and enhances collagen deposition. It can also relay changes in internal chemical signals into changes in its intrinsic luminescence for biphasic chemical sensing to prevent possible occurrence of skin hyperpigmentation caused by minocycline hydrochloride in wound therapy. Together with its ease of fabrication, high biocompatibility, high drug loading efficiency, and high release sustainability, CPS shows high potential to be developed into an intelligent solid-state device for wound treatment in the future.

Objective: To investigate the expression of TNF-a and NF-kB in the uterus of chronic pelvic inflammatory disease (CPID) model rats. Methods: 40 female rats that adaptive fed for 5 days were randomly divided into normal group, model group, high dose group, medium dose group and low dose group. In addition to the normal group, the rats in each group were made chronic pelvic inflammatory model by mechanical injury combined with implantation of bacteria. The rats in each group were administrated by gavage for 20 days. After the last administration, the level of TNF-a and NF-kB in serum was measured by ELASA method. Results: (1) after the establishment of the model, the uterus of the chronic pelvic inflammatory model rats showed the pathological damage of chronic inflammation; the levels of TNF-a and NF-kB in serum were higher than those in the normal group, the difference was statistically significant (P

An approach to synthesizing silver nanoparticles(AgNPs)using a Fusarium graminarum fungus was established in the present study.These nanoparticles are identified with the following techniques to confirm the form, size, and other physical properties of the crystal:UV-Visible Spectroscopy(UV-Vis),where the AgNPs showed absorbance at 420 nm, while X-Ray Diffraction (XRD)showed diffraction peaks at(38.05°,4 nm).The experiment consisted of 40 mice divided into two groups, the first group of 20 mice was considered to be the control animals and the other group 20mice was 21day of treatment with a dose of AgNPs(0.1ml/ day).Microscopic examination of the kidney section showed lobulated glomeruli,a large area of hemorrhage, changes in degeneration, and inflammatory cell infiltration. Biometric changes of the renal corpuscle showed no significant difference between the study group,while Bowman’s capsule,Proximal,and distal convoluted tubules revealed increased significant differences between the two groups.

Although diesel airborne particulate matter (PM2.5) has been known to play a role in many human diseases, there is no direct evidence that therapeutic drugs or proteins can diminish PM2.5‐induced diseases. Nevertheless, studies examining the negative control mechanisms of PM2.5‐induced diseases are critical to develop novel therapeutic medications. In this study, the consensus PDZ peptide of ZO‐1 inhibited PM2.5‐induced inflammatory cell infiltration, pro‐inflammatory cytokine gene expression, and TEER in bronchoalveolar lavage (BAL) fluid and AM cells. Our data indicated that the PDZ domain in ZO‐1 is critical for regulation of the PM2.5‐induced inflammatory microenvironment. Therefore, the PDZ peptide may be a potential therapeutic candidate during PM‐induced respiratory diseases.

The purpose of this study was to evaluate 210 periapical lesions with a newly created Dental Apical Inflammation Score/DAIS with regard to their inflammatory cell infiltration, bone tissue, epithelium, bacteria and foreign material.Specimens were obtained from 51 different dental practices over a period of 11 months. These specimens were then sent in for histopathological routine diagnostics.The DAIS classified 81 cases of Type 1 (acute inflammation = low, chronic inflammation = low), 79 cases of Type 2 (acute inflammation = low, chronic inflammation = high), 46 cases of Type 3 (acute inflammation = high, chronic inflammation = low) and 4 cases of Type 4 (acute inflammation = high, chronic inflammation = high). Bone tissue was found in 141 cases, signs for bacterial osteitis in 49 cases, cyst epithelium in 40 cases and foreign material in 27 cases. In 210 cases, cyst epithelium was evident in 27.2 % of Type 1, 15.2 % of Type 2, 8.7 % of Type 3 and in 50 % of Type 4 (p = .019). The 141 cases containing bone tissue showed signs of bacterial osteitis in 16.1 % of Type 1, 29.8 % of Type 2, 77.8 % of Type 3 and in 100 % of Type 4 (p.001). In 64 cases, Bacteria was evident in 30 % of Type 1, 25 % of Type 2, 55 % of Type 3 and in 100 % of Type 4 (p = .013).The DAIS could classify apical lesions with statistically significant differences. Bacterial osteitis in apical lesions was reported for the first time.

Brotowali (BR) extract (Tinospora crispa) can be used as an antimalarial. Aim: to determine the effect of BR extract in histopathological and expression of NFκB in mice tubules infected by Plasmodium berghei treated by artesunate (AR). Method: we used 42 C57BL / 6J strain mice as experimental animals, which were randomly divided into 7 groups : negative control (NC), positive control (PC), treatment group consist of AR 32 mg/kb (group 1); BR 70 mg/kg (group 2), combination of AR+BR 50 mg/kg (group 3), AR+BR 60 mg/kg (group 4), and AR+BR 70 mg/kg (group 5).  Histological examination (hematoxylin-eosin (HE) staining) and expression of NFKB (immunohistochemical staining) in the kidneys were performed on 7th and 14th. Result: compared to PC group, BR with doses of 70 mg until 14th day, improved the degree of tubular necrosis, interstitial fibrosis, tubular degeneration, and inflammatory cell infiltration (p

Most systemic lupus erythematosus (SLE) patients are photosensitive and ultraviolet B light (UVB) exposure worsens cutaneous disease and precipitates systemic flares. The pathogenic link between skin disease and systemic exacerbations in SLE remains elusive. Since the type I interferon (IFN-I) signature is detected in both the blood and skin of SLE patients and because cell injury through radiation therapy activates the cytosolic DNA sensor, cGAS, we asked whether UVB stimulated IFN-I through the cGAS pathway in vivo. In an acute model of UVB-triggered inflammation, we observed that a single exposure triggered an IFN-I signature not only in the skin, but also in the blood and kidneys. Early IFN-I response in the skin was almost entirely, and in the blood partly, dependent on the presence of cGAS, as was skin inflammation. Inhibition of cGAMP hydrolysis augmented the UVB-triggered IFN-I response. UVB skin exposure leading to cGAS-activation and IFN-I production could contribute to acute flares of disease in SLE.

Magnesium (Mg) is an emerging degradable metal for orthopaedics and its degradation product, Mg2+, has been reported to positively affect osteogenesis. Porous hydroxyapatite (HA) has been extensively studied for bone regeneration, but its slow degradation is an important factor limiting its uses. Therefore, we studied the combination of Mg and HA to integrate the advantages of the two materials while circumventing their disadvantages, with the aim of determining the optimum Mg/HA ratio. Surface-treated Mg particles (Φ ∼ 1.3 mm) and HA spheres (Φ ∼ 1.4 mm) were mixed at 0, 10, 30, and 50% (v/v). The mixtures were filled in titanium cages to form complexes. In vitro biocompatibility was studied by culturing MC3T3-E1 osteoblasts in extracts prepared from the complexes. In vivo biocompatibility and osteoinduction were evaluated by implantation in canine dorsal muscles. All complexes were not cytotoxic to the osteoblasts, regardless of the Mg proportion. Eight weeks after implantation in muscles, complexes containing 50% Mg showed inflammatory cell infiltration, whereas all other groups showed no evident inflammatory response. Additionally, complexes containing 30% Mg had significantly higher new bone area percentage (BV/TV), trabecular number (Tb.N), and bone growth rate than those containing 0, 10%, or 50% Mg. In comparison, complexes containing 50% Mg had significantly lower BV/TV and Tb.N than all other groups, and also had a significantly lower bone growth rate than those containing 10% or 30% Mg. Sixteen weeks after implantation, the trend in bone formation was similar to that observed at week 8. This shows that metallic Mg affected the osteoinductivity of HA-Mg complexes in a dose-dependent manner. In the present model, 30% Mg induced optimum osteoinduction. More studies are needed to explore the optimum Mg fractions for other implantation sites or forms of use.

Background: Bronchoscopic therapies are less invasive alternatives of surgical lung volume reduction for severe emphysema. Bending of lung tissue by implanting metallic coils into bronchi is one of the procedures. A new-designed device with a similar rationale, Reverser, has been developed with some improvements. Objectives: The aim of the study was to evaluate the safety and feasibility of the Reversers. Methods: Twelve healthy pigs were randomly divided into 3 groups (groups A, B, and C). The Reversers were implanted bronchoscopically into the selected airways using a proprietary delivery system. Physical examination, chest fluoroscopy, computed tomography (CT) scans, and bronchoscopic observations were performed before implantation and during the follow-up period. Necropsy was performed respectively at 1 month (group A), 3 months (group B), and 6 months (group C) after implantation. Results: A total of 47 Reversers were implanted successfully. The procedure was feasible and well tolerated by all pigs. No severe complications, such as pneumothorax, abscesses, and airway hemorrhage, were found. No unintended injuries or death occurred. Mild granulation and inflammation were observed in the airway wall. Opacities around Reversers were shown on CT scans in some pigs. In the pigs with opacities, histological evaluation revealed widened alveolar septa due to inflammatory cell infiltration in the vicinity of the Reversers. On the analysis of CT data, there was a trend for volume reduction of the treated lung at 1 and 3 months after treatment compared with baseline. Conclusions: This study showed that Reversers were safe and feasible for bronchoscopic lung volume reduction in pigs.

Background: The platelet-rich fibrin (PRF) has proven an immense role in angiogenesis and epithelization in a wound healing process. The present study aims to ascertain PRF's beneficial role in wound healing after depigmentation surgery. Materials and Methods: A total of 12 systemically healthy controls included were divided into two groups after scalpel depigmentation procedure. PRF was prepared according to Choukroun's standard protocol. Using split-mouth design after depigmentation, one group received PRF membrane, and in second group non-eugenol periodontal dressing was placed. The participants were evaluated for visual analog scale (VAS), healing index (HI) on 3rd and 5th day. Epithelization test using toluidine blue and histological examination employing punch biopsy was done on the 5th day. Results: On statistical scale, VAS, HI, epithelization test, and histological findings were statistically significant in the two study groups. PRF group proved better epithelization test and inflammatory cell infiltration was less in PRF group which confirmed superior wound healing in the group. Conclusion: PRF membrane postdepigmentation provided satisfactory patient comfort and enhanced the wound healing cascade.

Objective: The objective of this study is to evaluate the feasibility and safety of high-intensity focused ultrasound (HIFU) for ablation of swine pancreas and to detect the pathological variations in pancreas damage. Materials and Methods: (a) Eight swine were involved and randomly divided into two groups (Group A and B). HIFU was applied on swine in both groups for in vivo ablation of pancreas. The animals were anesthetized, and the artificial acoustic window was built. Then, the irradiation of FEP-BY02 type HIFU on pancreas was applied. (b) Swine in Group A were euthanized immediately after treating with HIFU to examine variations in pancreas. The biochemical evidence of pancreatitis was evaluated by blood samples collected from swine in Group B before and after HIFU. Then, the pancreas of swine in Group B was euthanized on day 5 after treatment to examine the pancreas. All specimens were visually inspected for both ultrasonic focal damage region (UFDR) and pathological routine by a skilled pathologist. Results: (a) The vital signs of all animals were stable during HIFU treatment and recovered well after treatment. (b) UFDR were observed in all HIFU irradiation region of the specimens, without significant size difference between the two groups. The coagulation nucleus pyknosis, cytochylema vacuolation, and nucleus membrane disruption were observed after HIFU in both groups. Membranous structure dissolution and inflammatory cell infiltration were also found after HIFU in swine of Group B. (c) There was no significant difference in the levels of blood amylase in swine of Group B before and after HIFU treatment. Conclusions: It was feasible and safe to use HIFU for ablation of the pancreas in swine.

BACKGROUND: Recently, new calcium silicate bioceramic sealers were introduced to the market. The selection of root canal sealers should not only be based on the different physical parameters but also on local biocompatibility and tissue tolerance. AIM: This study aimed to evaluate and compare the in-vivo biocompatibility of a BioRoot RCS in parallel to MTA Fillapex and AH Plus sealers. METHODS: Polyethylene tubes containing the freshly mixed test materials were implanted in the subcutaneous tissue of 32 Wistar rats. Empty tubes served as negative controls. After 7, 14, 30, and 60 days, the animals were sacrificed, and the implants with surrounding tissues were processed for routine histological analysis. Histological sections were analyzed under light microscopy. The tissue response was determined by the inflammatory cell infiltration intensity and the fibrous capsule thickness. RESULTS: Results revealed a statistically significant decrease of the inflammation intensity by time within each group for all tested sealers and control. A well-defined thin capsule was observed for all tested sealers at 60 days. CONCLUSION: BioRoot RCS exhibited rapid recovery of inflammation similar to controls. Thus, within the limitations of this study, it can be considered a biocompatible sealer with acceptable tissue tolerance.

Introduction: Previous studies have reported robust inflammatory cell infiltration, selective synthesis of IgG, B-cell clonal expansion, and deposition of immune complexes and complement within Cerebral Cavernous Malformation (CCM) lesions. Furthermore,B-cell depletion has been shown to reduce the maturation of CCM in murine models. We hypothesize that specific autoantigen(s) within the lesional milieu trigger the pathogenetic immune responses in CCMs. This study aims to identify those putative autoantigen(s) using recombinant antibodies (rAbs) derived from plasma cells found in surgical human CCM lesions. Methods: CD138 + plasma cells were laser captured from fresh frozen surgically resected human CCM lesions. Clonally expanded immunoglobulin heavy- and light-chain variable region pairs were cloned into IgG expression vectors and expressed as monoclonal antibodies. Purified rAbs were assayed by immunofluorescence with CCM lesion tissue and normal brain tissue sections. rAbs assayed by immunocytochemistry with human primary cell line were used to further define the staining pattern. The cell lysates were immunoprecipitated with rAb, after protein purification by SDS-PAGE, and analyzed by Mass spectrometry. Results: In normal brain tissue, rAbs stained endothelial cells with limited staining of glial cells. In CCM lesional tissue, rAbs stained endothelial cells, glial cells as well as structures in the acellular matrix adjacent to caverns. In cultured Human Brain Microvascular Endothelial Cells (HBMECs) and Human Astrocytes (HAs), rAbs co-localized with cytoplasmic components. After HBMEC and HA cell lysates were immunoprecipitated with rAb, a Coomassie Stain detected bands of approximately 50 kDa. Conclusions: Our results suggest that autoantigen(s) in human CCM lesions are cytoplasmic components present in lesional tissue as well as in normal brain tissue. Molecular level identification of the triggering antigen is still ongoing by mass spectrometry. Identification of the autoantigen(s) in the lesional milieu might explain the propensity of lesion development from leaky endothelium in the neuroglial parenchyma. Characterization of the autoantigen triggers will open new venues for therapy or vaccine in this disease.

The present study aims to investigate the effects of CCR3 gene knockout in bone marrow cells (CCR3-KO) on the mouse model of combined allergic rhinitis and asthma syndrome (CARAS). It was found that CCR3-KO significantly reduced eosinophil (EOS) migration into the nasal (NALF) and bronchoalveolar (BALF) cavities of mice, and decreased Th2 cytokines (such as, IL-4, IL-5 and IL-13) levels in nasal mucosa and lung tissues. In addition, histological analysis showed that the damage degree of nasal mucosa structure in ovalbumin (OVA) modulated CCR3-KO mice was significantly less than that in OVA modulated Wild type (WT) mice, with reduced inflammatory cell infiltration and nasal mucus secretion. The infiltration of inflammatory cells in lung tissue was significantly reduced, and the proliferation of lung smooth muscle layer and extracellular matrix (ECM) production were decreased. Symptom analysis showed that CCR3-KO can reduced allergic rhinitis (AR) signals as nose scratching and sneezing. It was also found CCR3-KO reduce OVA-induced weight loss. The results showed that CCR3-KO could reduce the symptoms of allergic inflammation in CARAS mice by reducing airway inflammatory cell infiltration and down-regulating the expression of Th2 cytokines, and CCR3 gene could be used as a target gene for the treatment of CARAS.

The initial symptoms of Crohn's disease (CD) sometimes present as extraintestinal lesions, which can be a diagnostic challenge for physicians. Painful legs, known as "gastrocnemius myalgia syndrome", are rare complications that often precede abdominal manifestations. We herein report the case of a 38-year-old man who presented with bilateral leg myalgia lasting for 4 months. Magnetic resonance imaging showed abnormal intensity, and a muscle biopsy revealed inflammatory cell infiltration. Abdominal symptoms appeared three months after the myalgia onset, and the diagnosis of CD was confirmed later by endoscopic and radiological findings. To our knowledge, this is the first description of gastrocnemius myalgia syndrome in Japan.

Telogen effluvium is categorized in nonscarring alopecia, which shows scalp hair thinning and shedding diffusely resulting from inducing factors such as physiological stressful events and several acute or chronic diseases. It usually appears in female patients following parturition, as well as after febrile disease, major surgery, emotional stress, abrupt diet, chronic illness, or the taking of certain medication pills. Two patients who both recalled an operational history of hair transplantation visited our department with their frontal and both temporal hair loss. Physical examination of the both patients showed localized but diffuse hair loss, especially in the frontal and temporal scalp. Histopathological examination of biopsy specimen taken from their temporal scalp revealed normal follicular density and increased numbers of telogen hair follicles without any inflammatory cell infiltration around follicles. These clinical and histopathological findings were consistent with telogen effluvium. Both of them were reassured and placed on close follow-up without any treatment. From these cases, we demonstrate that localized telogen effluvium could be a cause of hair loss after hair transplantation.

Developing an efficient and available material for improved cutaneous tissue regeneration is a major challenge in healthcare. Inspired by the concept of moist wound healing, the injectable and self-healing adenine-modified chitosan (AC) hydrogels are designed to significantly accelerate wound healing without the addition of therapeutic drugs. A series of AC derivatives with degree of substitution (DS) ranging from 0.21 to 0.55 were synthesized in aqueous solutions, and the AC hydrogels were prepared by a simple heating/cooling process. AC hydrogels presented good self-healing, low swelling rate capacity, biocompatibility, promote cell proliferation and excellent hemostatic effect. The hydrogels displayed excellent antibacterial activities against gram-negative bacteria, gram-positive bacteria, fungi and drug-resistance bacteria. Moreover, the full-thickness skin defect model experiments showed that AC hydrogels could reduce inflammatory cell infiltration and accelerate wound healing significantly. The hydrogel can shed new light on designing of the multifunctional dressings for wound healing.